Association of p53 codon 72 polymorphism with advanced lung cancer: the Arg allele is preferentially retained in tumours arising in Arg/Pro germline heterozygotes

Abstract

The association of p53 codon 72 polymorphism with cancer has been investigated by several scientific groups with controversial results. In the present study, we examined the genotypic frequency of this polymorphism in 54 patients with advanced lung cancer and 99 normal controls from the geographical region of Greece. Sputum and bronchial washing samples from each patient were assayed for the presence of human papillomavirus. Codon 72 heterozygous (Arg/Pro) patients were also analysed for loss of heterozygosity at the TP53 locus, in order to determine the lost p53 allele (Arg or Pro). p53 Arg/Arg genotype was significantly increased in lung cancer patients compared to normal controls (50% vs 24.2%, P50.002). Human papillomavirus was detected only in two patients (3.7%). Loss of heterozygosity at the TP53 locus was found in 14 out of 27 Arg/Pro patients (51.85%). The Pro allele was lost in 11 cases (78.6%), while the Arg allele was lost in three (21.4%). Our results suggest that p53 codon 72 Arg homozygosity is associated with advanced lung cancer, and that the Arg allele is preferentially retained in patients heterozygous for this polymorphism. On the other hand, human papillomavirus infection does not seem to play an important role in lung carcinogenesis.

Association of p53 codon 72 polymorphism with liver metastases of colorectal cancers positive for p53 overexpression

“…Several reports indicated that the 72R allele is preferentially mutated and retained in various human tumors (Kawaguchi et al, 2000;Marin et al, 2000;Tada et al, 2001;Langerod et al, 2002;Papadakis et al, 2002;Anzola et al, 2003;Schneider-Stock et al, 2004a;Hsieh et al, 2005), and is associated with the presence of p53 overexpression (Lee et al, 2006). In experiments, mutant 72R allele tended to block p73 function more effectively than mutant 72P isoform, which might lead to a higher tendency of p53 mutation in tumors .…”

“…The 72R allele of mutant p53 has been found to have greater ability to bind p73, neutralizing p73-induced apoptosis, when compared to the mutant 72P allele . Moreover, the 72R allele is preferentially mutated and retained in various human tumors arising in RP germline heterozygotes Kawaguchi et al, 2000;Tada et al, 2001;Langerod et al, 2002;Papadakis et al, 2002;Anzola et al, 2003;Schneider-Stock et al, 2004a;Hsieh et al, 2005). Recently a positive association of the 72R allele with p53 overexpression has been reported in esophageal cancer tissue (Lee et al, 2006).…”

Biological significance of allele specific loss of the p53 gene in breast carcinomas

“…This phenomenon has also been seen in colorectal cancer [15], squamous cell carcinomas [20], ovarian carcinomas 123 [21], and lung cancer [22], as well as in cancers involving esophagus, and the urinary tract [23,24]. The biological significance of these univocal findings seems unclear.…”

Estudo do polimorfismo genético no gene p53 (códon 72) em câncer colorretal

“…O polimorfismo ocorre por simples substituição de uma base no códon que resulta em alteração estrutural da proteína p53 (24) . Vários autores têm demonstrado que a presença de Arg/Arg confere maior risco de desenvolvimento de tumores, como em cânceres de bexiga, cérvix uterino (22) , mama (16) , pulmão (17) , etc. Entretanto, no câncer colorretal não há uma associação clara com este polimorfismo e aumento do risco de câncer (10) .…”